[Federal Register: April 2, 2009 (Volume 74, Number 62)]
[Notices]
[Page 15063-15066]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr02ap09-127]
[[Page 15063]]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF VETERANS AFFAIRS
Determination of Presumption of Service Connection Concerning
Illnesses Discussed in National Academy of Sciences Report on Gulf War
and Health: Volume 5: Infectious Diseases
AGENCY: Department of Veterans Affairs.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: As required by law, the Department of Veterans Affairs (VA)
hereby gives notice that the Secretary of Veterans Affairs, under the
authority granted by the Persian Gulf War Veterans Act of 1998, Public
Law 105-277, title XVI, 112 Stat. 2681-742 through 2681-749 (codified
in part at 38 U.S.C. 1118), has determined that there is no basis to
establish a presumption of service connection for Al Eskan disease,
idiopathic acute eosinophilic pneumonia, wound and nosocomial
infection, mycoplasmas, as discussed in the October 2006 report of the
National Academy of Sciences, titled ``Gulf War and Health Volume 5:
Infectious Diseases'', or for any illness based on exposure to
biologic-warfare agents during service in the Persian Gulf during the
Persian Gulf War.
FOR FURTHER INFORMATION CONTACT: Thomas Kniffen, Chief, Regulations
Staff (211D), Compensation and Pension Service, Veterans Benefits
Administration, Department of Veterans Affairs, 810 Vermont Avenue,
NW., Washington, DC 20420, (202) 461-9725.
SUPPLEMENTARY INFORMATION:
I. Statutory Requirements
The Persian Gulf War Veterans Act of 1998, Public Law 105-277,
title XVI, 112 Stat. 2681-742 through 2681-749 (codified at 38 U.S.C.
1118), and the Veterans Programs Enhancement Act of 1998, Public Law
105-368, 112 Stat. 3315, directed the Secretary to seek to enter into
an agreement with the National Academy of Sciences (NAS) to review and
evaluate the available scientific evidence regarding associations
between illnesses and exposure to toxic agents, environmental or
wartime hazards, or preventive medicines or vaccines to which service
members may have been exposed during service in the Persian Gulf during
the Persian Gulf War. Congress directed the NAS to identify agents,
hazards, medicines, and vaccines to which service members may have been
exposed during service in the Persian Gulf during the Persian Gulf War.
Congress mandated that the NAS determine, to the extent possible:
(1) Whether there is a statistical association between exposure to the
agent, hazard, medicine, or vaccine and the illness, taking into
account the strength of the scientific evidence and the appropriateness
of the scientific methodology used to detect the association; (2) the
increased risk of illness among individuals exposed to the agent,
hazard, medicine, or vaccine; and (3) whether a plausible biological
mechanism or other evidence of a causal relationship exists between
exposure to the agent, hazard, medicine, or vaccine and the illness.
Section 1118 of Title 38 of the United States Code provides that
whenever the Secretary determines, based on sound medical and
scientific evidence, that a positive association (i.e., the credible
evidence for the association is equal to or outweighs the credible
evidence against the association) exists between exposure of humans or
animals to a biological, chemical, or other toxic agent, environmental
or wartime hazard, or preventive medicine or vaccine known or presumed
to be associated with service in the Southwest Asia theater of
operations during the Persian Gulf War and the occurrence of a
diagnosed or undiagnosed illness in humans or animals, the Secretary
will publish regulations establishing presumptive service connection
for that illness. If the Secretary determines that a presumption of
service connection is not warranted, he is to publish a notice of that
determination, including an explanation of the scientific basis for
that determination. The Secretary's determination must be based on
consideration of the NAS reports and all other sound medical and
scientific information and analysis available to the Secretary.
Although section 1118 does not define ``credible evidence,'' it
does instruct the Secretary to consider whether the results (of any
report, information, or analysis) are statistically significant, are
capable of replication, and withstand peer review. See 38 U.S.C.
1118(b)(2)(B). Simply comparing the number of studies that report a
significantly increased relative risk to the number of studies that
report a relative risk that is not significantly increased is not a
valid method for determining whether the weight of evidence overall
supports a finding that there is or is not a positive association
between exposure to an agent, hazard, medicine, or vaccine and the
subsequent development of the particular illness. Because of
differences in statistical significance, confidence levels, control for
confounding factors, and other pertinent characteristics, some studies
are clearly more credible than others, and the Secretary gives the more
credible studies more weight in evaluating the overall weight of the
evidence concerning specific illnesses.
II. Prior National Academy of Sciences Reports
The NAS issued its initial report titled, Gulf War and Health,
Volume 1: ``Depleted Uranium, Sarin, Pyridostigmine Bromide,
Vaccines,'' on January 1, 2000. In that report, NAS limited its
analysis to the health effects of depleted uranium, the chemical
warfare agent, sarin, vaccinations against botulism toxin and anthrax,
and pyridostigmine bromide, which was used in the Persian Gulf War as a
pretreatment for possible exposure to nerve agents. On July 6, 2001, VA
published a notice in the Federal Register announcing the Secretary's
determination that the available evidence did not warrant a presumption
of service connection for any disease discussed in that report. See 66
FR 35702 (2001).
The NAS issued its second report titled, ``Gulf War and Health,
Volume 2: Insecticides and Solvents,'' on February 18, 2003. In that
report, the NAS focused on the health effects of insecticides and
solvents that were shipped to the Persian Gulf during the Persian Gulf
War. The pesticides considered by the NAS were organophosphorous
compounds (Malathion, diazinon, chlorpyrifos, dichlorvos, and
azamethiphos), carbamates (carbaryl, propoxur, and methomyl),
pyrethrins and pyrethyroids (permethrin and d-phenothrin), lindane, and
N,N-diethyl-3-methylbenzamide (DEET). The NAS considered 53 solvents in
eight groups: aromatic hydrocarbons (including benzene), halogenated
hydrocarbons (including tetrachloroethylene and dry-cleaning solvents),
alcohols, glycols, glycol esters, esters, ketones, and petroleum
distillates. On August 24, 2007, VA published a notice in the Federal
Register announcing the Secretary's determination that the available
evidence did not warrant a presumption of service connection for any
disease discussed in that report. 72 FR 48734 (2007).
The NAS issued an update on sarin in a report titled ``Gulf War and
Health: Updated Literature Review of Sarin,'' on August 20, 2004. In
that report, the NAS focused on the long-term health effects from
exposure to the nerve agent, sarin. VA published a Federal Register
Notice announcing the Secretary's determination that it was not
necessary to establish new presumptions of
[[Page 15064]]
service connection for any diseases based on the updated findings on
long-term health effects from sarin. 73 FR 42411 (2008).
The NAS issued its third report, titled ``Gulf War and Health,
Volume 3: Fuels, Combustion Products, and Propellants,'' on December
20, 2004. In that report, the NAS focused on the health effects of
hydrazines, red fuming nitric acid, hydrogen sulfide, oil-fire
byproducts, diesel-heater fumes, and fuels (for example, jet fuel and
gasoline). VA published a Federal Register Notice announcing the
Secretary's determination that the available evidence did not warrant a
presumption of service connection for any disease discussed in that
report. 73 FR 50856 (2008).
The NAS issued its fourth report, titled ``Gulf War and Health
Volume 4. Health Effects of Serving in the Gulf War,'' on September 12,
2006. In that report the NAS focused on the health status of veterans
of the 1991 Gulf War. The report was intended to inform VA about
illnesses and clinical issues including possible relevant treatments,
which might have been overlooked among this population, regardless of
the specific underlying cause. VA is drafting a Federal Register notice
announcing the Secretary's determination that the available evidence
does not warrant a presumption of service connection for any disease
discussed in that report.
III. Gulf War and Health, Volume 5: Infectious Diseases
The NAS committee issued its fifth report, titled ``Gulf War and
Health Volume 5: Infectious Diseases'' on October 16, 2006. The
committee reviewed published, peer-reviewed scientific and medical
literature on long-term health effects from infectious diseases
associated with Southwest Asia. Based on the NAS's report, VA is
currently drafting a proposed rule to establish presumptive service
connection for nine infectious diseases discussed in the report and
providing guidance regarding long-term health effects associated with
these diseases.
However, the NAS additionally discussed several infectious diseases
and agents that had been identified as possible causes of illnesses in
veterans with service in Southwest Asia or that otherwise presented
issues of special interest to such veterans. This notice provides the
Secretary's determination that the scientific evidence in the report
does not warrant a presumption of service connection for any illnesses
caused by these diseases and agents. The diseases and agents are Al
Eskan disease, idiopathic acute eosinophilic pneumonia, wound and
nosocomial infection, mycoplasmas, and biologic-warfare agents.
Al Eskan Disease
Al Eskan disease is named after a village in Saudi Arabia where
U.S. military personnel lived during the 1991 Gulf War. These soldiers
reported a vague systemic illness causing primarily respiratory
symptoms that was termed Al Eskan disease or Desert Storm pneumonitis
in three studies: Korenyi-Both et al. 1992; Korenyi-Both et al. 1997;
Korenyi-Both et al. 2000. During Operation Desert Shield (ODSh) and
Operation Desert Storm (ODSt), approximately 697,000 troops were
deployed. Although researchers are unable to determine the exact number
of troops affected by Al Eskan disease, data on respiratory illnesses
in troops reveal that respiratory symptoms in general were more common
in those with a history of lung disease, smoking, and longer
deployment; more common in those with less outdoor exposure; more
common in those with less outdoor exposure; and were most prominent in
personnel who slept in air-conditioned facilities. Al Eskan disease or
a similar illness has not been reported in troops deployed to Operation
Iraqi Freedom (OIF) or Operation Enduring Freedom (OEF).
Al Eskan disease was first reported in 1992, and was characterized
by sudden or insidious onset of chills, fever, sore throat, hoarseness,
nausea and vomiting, and generalized malaise followed by respiratory
tract complaints which included increasingly severe dry cough or
expectoration of tan sputum (Korenyi-Both et al. 1992). The disease
appears to be self-limited, and physical findings are minimal. Systemic
description and precise definition of Al Eskan disease are unavailable.
Korenyi-Both and colleagues have ascribed Al Eskan disease to an
immune response to sand-particle exposure, and argued that Al Eskan
disease is most likely a form of acute silicosis aggravated by the
pulmonary immune response and perhaps other genetic and environmental
factors (Korenyi-Both et al. 1992; Korenyi-Both et al. 1997; Korenyi-
Both et al. 2000). There are no clinical data to support this
hypothesis and no reports of chronic lung disease consistent with
silicosis in veterans. The hypotheses and conclusions of these
researchers have not been uniformly accepted and have generated
considerable debate (Clooman et al. 2000; Kilpatrick 2000).
The NAS found that no data link Al Eskan disease to any specific
chronic illness. Further, there is no evidence that the syndrome or
disease observed in troops in Al Eskan village was caused by a
communicable microbial pathogen. Koryeni-Both et al. have argued that
the disease is caused by exposure to the unique sand dust of the
central and eastern Arabian Peninsula and in particular to the silica
in the sand. However, more than 13 years have passed since the initial
description of Al Eskan disease appeared in the literature, and
researchers have been unable to link chronic respiratory diseases in
military personnel to exposure to Persian Gulf sand.
Based on the NAS report, the Secretary has determined that there is
insufficient evidence to conclude that there is a positive association
between the condition described as Al Eskan disease and exposure to an
agent, hazard, preventive medicine or vaccine associated with Gulf War
service. To the extent the described condition involves respiratory
symptoms of unknown etiology, current VA regulations provide a
presumption of service connection for chronic disability due to
undiagnosed illness manifest by respiratory signs and symptoms. See 38
CFR 3.317.
Idiopathic Acute Eosinophilic Pneumonia
Idiopathic Acute Eosinophilic Pneumonia (IAEP) is a syndrome
characterized by a febrile illness, diffuse pulmonary infiltrates, and
pulmonary eosinophilia (Allen et al. 1989; Badesch et al. 1989; Philit
et al. 2002). Patients with IAEP have no history of asthma, allergy, or
chronic lung disease and no discernible infection. Patients with IAEP
present with fever, diffuse pulmonary infiltrates, cough, shortness of
breath, and, not infrequently, respiratory failure. Most IAEP patients
who survive the acute illness make a complete recovery. Eighteen
soldiers deployed to Southwest Asia in OIF developed IAEP.
In many cases, IAEP has been associated with cigarette smoking and
exposure to dust (Badesch et al. 1989; Pope-Harman et al. 1996; Rom et
al. 2002). No causative pathogens were detected or implied by the
immune repose of soldiers with IAEP (Allen et al. 1989; Shorr et al.
2004). Survey results failed to identify a common source of
environmental, drug, or toxin exposure (Shorr et al. 2004). IAEP would
not be expected to have long-term adverse health outcomes.
Based on the NAS report, the Secretary has determined that there is
insufficient evidence to conclude that there is a positive association
between IAEP and exposure to an agent, hazard,
[[Page 15065]]
preventive medicine, or vaccine associated with Gulf War service.
Wound and Nosocomial Infection
Soldiers can experience a wide variety of exposures to pathogens
from explosives or combat (wound infections) or in health-care settings
(nosocomial infections). One condition that is more prevalent in troops
in Southwest Asia than in civilian settings is infection with
Acinetobacter calcoaceticus-baumannii complex, a well-recognized cause
of wound infection in general and among military troops in particular
(CDC 2004; Davis et al. 2005). The complex is also a cause of
nosocomially-acquired infection when wounded, infected soldiers are
intermingled with other patients in the intensive care unit, emergency
room, or hospital ward.
Research data has also revealed that A. baumannii bacteremia was
common in OEF and OIF returnees who were hospitalized for injuries,
although it was rare before the state of OEF and OIF (CDC 2004; Davis
et al. 2005; Zapor and Moran 2005), and that nearly any war-theater
injury, whether combat-derived or otherwise, may result in infection.
The risk of infection is inherent in military service, training,
readiness activities, transport, or combat (Zapor and Moran 2005).
Both wound infections and nosocomial infections are hazards for
U.S. personnel deployed to Southwest Asia. Given modern medical and
surgical treatment and the ability to evacuate injured military
personnel rapidly, most infections will be seen within days or weeks of
wounds.
The NAS found that both wound infections and nosocomial infections
manifest within a short period after injury or exposure, such that
making an epiodemiological link between a particular infection and the
precipitating wound or exposure is rarely difficult. The NAS further
noted that, in rare cases, infections associated with chronic
osteomyelitis could go undetected and become manifest after service,
although it noted a ``near absence'' of case reports documenting that
occurrence. In view of the possibility of infections from other
military and civilian sources outside of Gulf War service, the NAS
stated that determining whether any infections manifest after service
were associated with such service or with other causes would require
case-by-case evaluations of the epidemiologic, clinical, and
microbiological characteristics of the infection.
Based on the NAS report, the Secretary has determined that there is
insufficient evidence to conclude that there is a positive association
between wound or nosocomial infections manifest after service and any
exposure to an agent, hazard, preventive medicine, or vaccine
associated with Gulf War service. Any such infections manifest within
service or within a short period following an in-service wound or
exposure would be subject to service connection on a direct basis under
current law.
Mycoplasmas
Mycoplasmas are ubiquitous microorganisms found as commensal
colonizers and as pathogens in plants, insects, and animals. They are
pleomorphic and filamentous and have a deformable membrane, which
allows them to pass through filters that retain bacteria. They are
fastidious and difficult to culture on cell-free media; at the same
time, because of their common presence as nonpathogenic colonizers,
they are common contaminants of cell cultures. The propensity for
contamination of cell cultures can lead to false conclusions about the
association of mycoplasmas with a variety of clinical syndromes (Baum
2005).
Culture of Mycoplasma fermentans on cell-free media (which decrease
the risk of contamination) has been extremely difficult, and this has
led to controversy over whether the organisms are true pathogens or
merely contaminants.
The NAS noted that mycoplasmas are ubiquitous and did not suggest
that they are more prevalent in the Gulf War theater than in other
locations. However, it addressed mycoplasmas as a matter of special
interest to Gulf War veterans because certain researchers have
suggested that many of the symptoms of Gulf War illness could be
explained by aggressive mycoplasma infections present as contaminants
in vaccines administered to service members before deployment to the
Gulf.
Several studies by Nicolson and colleagues report a link between
Mycoplasma fermentans and health problems in Gulf War veterans
(Nicolson et al. 2002; Nicolson et al. 2003; Nicolson and Rosenberg-
Nicolson 1995; Nicolson and Nicolson 1996). Nicolson and colleagues
hypothesized that the source of such infections in Gulf War veterans
may have been contamination of the multiple vaccines received by troops
before and during deployment (Nicolson et al. 2003). It was suggested
that many of the symptoms of Gulf War illness could be explained by
``aggressive pathogenic mycoplasma infections, and they should be
treatable with multiple courses of antibiotics, such as doxycycline or
macrolides'' (Nicolson and Rosenberg-Nicolson 1995). However,
independent attempts to confirm the results of studies conducted by
Nicolson and his colleagues have been unsuccessful (Gray et al. 1999;
Lo et al. 2000). One report noted that the methodology used by Nicolson
and colleagues was ``an inappropriate diagnostic method for detection
of M. fermentans'' and that neither the specificity nor the sensitivity
of the test had been established (Dybvig 1998). Because of the
conflicting data related to M. fermentans infections and their possible
association with Gulf War illnesses and the suggestion of possible
benefits of treatment with doxycycline, VA conducted a randomized
placebo-controlled trial to determine whether doxycycline could improve
functional status of persons with Gulf War illness (Donta et al. 2004).
Overall, the results of this study revealed no statistically
significant difference between the doxycycline-treated and placebo
groups.
Although several studies by Nicolson and colleagues report a link
between Mycoplasma fermentans and health problems in Gulf War veterans
(Nicolson et al. 2002; Nicolson et al. 2003; Nicolson and Rosenberg-
Nicolson 1995; Nicolson and Nicolson 1996), other investigators were
not able to duplicate their work and there are concerns about the
nuclear gene tracking technique used by Nicolson et al. (Dybvig 1998;
Gray et al. 1999; Lo et al. 2000). After reviewing the evidence,
mycoplasma infection is not believed to be related to the symptoms
reported by Gulf War veterans.
Based on the NAS report, the Secretary has determined that there is
insufficient evidence to conclude that there is a positive association
between mycoplasma infections and any exposure to an agent, hazard,
preventive medicine, or vaccine associated with Gulf War service. The
evidence does not show that mycoplasma infections are associated with
Gulf War illness or any other chronic health outcome.
Biologic-Warfare Agents
Biologic warfare is defined as the use of microorganisms or toxic
products derived from microorganisms to inflict mass casualties in
military and civilian populations (Horn 2003). At the time of the 1991
Gulf War, Iraq had an active biologic warfare program. Iraq developed
bombs, missile warheads, aerosol generators, and helicopter and jet
spray systems for dispersal of biological warfare agents (Leitenberg
2001). Iraqi sources reported that aflatoxin, botulinum toxin, and
Bacillus anthracis were loaded in missiles and air-delivery bombs in
preparation for
[[Page 15066]]
the Gulf War (Roffey et al. 2002). Of the four biological warfare
agents that Iraqi sources reported weaponized: aflatoxin, botulinum
toxin, Bacillus anthracis, and ricin, only anthrax is a living
microorganism and capable of multiplying in infected people. However,
no evidence has been found that Iraq deployed any weapons containing
biological warfare agents (Roffey et al. 2002; Zilinskas 1997).
Based on the NAS report, the Secretary has concluded that a
presumption is not warranted for any disease associated with exposure
to biological warfare agents because such weapons were not shown to
have been deployed in the Gulf War.
IV. Conclusion
After careful review of the findings of the 2006 NAS report, ``Gulf
War & Health Volume 5: Infectious Diseases,'' the Secretary has
determined that the scientific evidence presented in the report and
other information available to the Secretary indicate that no new
presumption of service connection is warranted for Al Eskan disease,
idiopathic acute eosinophilic pneumonia, wound and nosocomial
infection, mycoplasmas, or for any illness based on exposure to
biologic-warfare agents.
Approved: March 26, 2009.
John R. Gingrich,
Chief of Staff, Department of Veterans Affairs.
[FR Doc. E9-7342 Filed 4-1-09; 8:45 am]